Identification of lncRNA biomarkers in hepatocellular carcinoma by comprehensive analysis of the lncRNA-mediated ceRNA network.

Growing evidence implicates that miRNAs can interact with long non-coding RNAs (lncRNAs) to regulate target mRNAs through competitive interactions. However, this mechanism that regulate tumorigenesis and cancer progression remains largely unexplored. Long non-coding RNAs (lncRNAs) act as competing endogenous RNAs (ceRNAs), which play a significant role in regulating gene expression. The purpose of our study was to determine potential lncRNA biomarkers to predict the prognosis of HCC by comprehensive analysis of a ceRNA network. The edgeR package was used to obtain the differentially expressed RNA datasets by analyzing 370 HCC tissues and 50 adjacent non-HCC tissues from The Cancer Genome Atlas (TCGA). Through investigating the differentially expressed between HCC tissues and adjacent non-HCC tissues, a total of 947 lncRNAs, 52 miRNAs, and 1,650 mRNAs were obtained. The novel constructed ceRNA network incorporated 99 HCC-specific lncRNAs, four miRNAs, and 55 mRNAs. Survival analysis identified 22 differentially expressed mRNAs, four miRNAs, and nine lncRNAs which were associated with overall survival (OS) time in HCC (p < 0.05), and further exploration was performed to assess the correlation of these differentially expressed genes with tumor stage. The Interpretation of the potential functions of these differentially expressed genes in HCC was realized by Gene ontology (GO) and KEGG pathway enrichment analyses. Seven lncRNAs were confirmed based on univariate Cox regression analysis, lasso COX regression analysis and multivariate Cox regression analysis to construct a predictive model in HCC patients which were related to the prognosis of OS. In summary, ceRNAs contributed to explore the mechanism of tumorigenesis and development, and a model with seven lncRNAs might be potential biomarker to predict the prognosis of HCC. These findings supported the need to studies on the mechanisms involved in the regulation of HCC by ceRNAs.

Tumor-Targeting NIRF/MR Dual-Modal Molecular Imaging Probe for Surgery Navigation.

Multimodality imaging recognized as a promising monitoring strategy can serve the needs of accurate diagnosis and treatment of cancer by providing molecular and anatomic information about tumor sites. However, the probes based on multiple imaging modalities for surgery navigation remain limited due to poor biocompatibility and tumor targeting specificity. Herein, we present a small-molecule near-infrared fluorescence/magnetic resonance (NIRF/MR) imaging probe, Gd-NMC-3, covalently coupled with DCDSTCY and Gd-DOTA via butane diamine, for precise detection and intraoperative visualization. The in vitro and in vivo studies demonstrated that Gd-NMC-3 could be effectively accumulated in tumor sites as a bimodal imaging molecule exhibiting significant fluorescence accumulation and reasonable relaxation property in tumors with low cytotoxicity and good biocompatibility. Furthermore, Gd-NMC-3 was successfully applied to provide real-time visual navigation in LM3 orthotopic and subcutaneous tumor models to guide the resection of tumors. Importantly, no more fluorescence was observed in mice after operation, implying the total removal of tumor tissues. In conclusion, Gd-NMC-3 has great potential to be applied in the clinic based on its high resolution and sensitivity in tumor imaging.

Manipulating Offense and Defense Signaling to Fight Cold Tumors with Carrier-Free Nanoassembly of Fluorinated Prodrug and siRNA.

Chemoimmunotherapy has shown great potential to activate an immune response, but the immunosuppressive microenvironment associated with T cell exhaustion remains a challenge in cancer therapy. The proper immune-modulatory strategy to provoke a robust immune response is to simultaneously regulate T-cell exhaustion and infiltration. Here, a new kind of carrier-free nanoparticle is developed to simultaneously deliver chemotherapeutic drug (doxorubicin, DOX), cytolytic peptide (melittin, MPI), and anti-TOX small interfering RNA (thymocyte selection-associated high mobility group box protein, TOX) using a fluorinated prodrug strategy. In this way, the enhanced immunogenic cell death (ICD) induced by the combination of DOX and MPI can act as "offense" signaling to increase CD8+ T-cell infiltration, while the decreased TOX expression interfered with siTOX can serve as "defense" signaling to mitigate CD8+ T-cell exhaustion. As a result, the integration of DOX, MPI, and siTOX in such a bifunctional system produced a potent antitumor immune response in liver cancer and metastasis, making it a promising delivery platform and effective strategy for converting "cold" tumors into "hot" ones.

Effects of Knowledge Hiding in Dual Teaching Methods on Students' Performance-Evidence From Physical Education Department Students.

With the post-pandemic situation, digitalization has revolutionized physical teaching into online teaching and has become a common practice. The engagement of students has been essential for their good academic performance which can be ensured by the active participation of the students and this is a real challenge for the teachers. However, sometimes in online and physical teaching, teachers are also involved in rationalized knowledge hiding, which leads to the disengagement of the students, and this ultimately affects their academic performance. Therefore, the present study aims at measuring the students' disengagement in the teaching classes, both physical and online. The population of the present study is the students from the universities of China belonging to different fields of study. The sample size for this study is 246. The data are obtained through the Questionnaire surveys. The existing study has assessed the role of teachers' rationalized knowledge hiding behaviors in the disengagement of students and their lesser grades. It has been found that rationalized knowledge hiding in online teaching does not affect students' performance; however, it makes students disengage from their studies in physical classes. Interestingly, the rationalized knowledge hiding in physical teaching has negatively affected the performance of the students. Furthermore, the mediating role of the students' disengagement has been found significant in this study. Organizations, especially universities, can ensure maximum knowledge sharing by motivating the instructors through positive reinforcements. This study will be useful for the curriculum coordinators of different departments in ensuring the maximum outcome of the teaching classes, workshops, and seminars conducted either physically or online to avoid the rationalized knowledge hiding of the teachers.

A New Risk Score Based on Eight Hepatocellular Carcinoma- Immune Gene Expression Can Predict the Prognosis of the Patients.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the malignant tumors with high morbidity and mortality worldwide. Immunotherapy has emerged as an increasingly important cancer treatment modality. However, the potential relationship between immune genes and HCC still needs to be explored. The purpose of this study is to construct a new prognostic risk signature to predict the prognosis of HCC patients based on the expression of immune-related genes (IRGs) and explore its potential mechanism. METHODS: We analyzed the gene expression data of 332 HCC patient samples and 46 adjacent normal tissues samples (Solid Tissue Normal including cirrhotic tissue) in The Cancer Genome Atlas (TCGA) database and clinical characteristics. We analyzed the gene expression data, identified differentially expressed IRGs in HCC tissues, filtered IRGs with prognostic value to construct an IRG signature, and classified patients into high and low gene expression groups based on the expression of IRGs in their tumor tissues. We also investigated the potential molecular mechanisms of IRGs through a bioinformatics approach using Protein-Protein Interaction (PPI) network, Kyoto Encyclopedia of Genes and Genomes (KEGG) database analysis and Gene Ontology (GO) database analysis. Differentially expressed IRGs associated with significant clinical outcomes (SIRGs) were identified by univariate Cox regression analysis. An immune-related risk score model (IRRSM) was established based on Lasso Cox regression analysis and multivariate Cox regression analysis. Based on the IRRSM, the immune score of the patients was calculated, and the patients were divided into high-risk and low-risk patients according to the median score, and the differences in survival between the two groups were compared. Then, the correlation analysis between the IRRSM and clinical characteristics was performed, and the IRRSM was validated using the International Cancer Genome Consortium (ICGC) database. RESULTS: The IRRSM was eventually constructed and confirmed to be an independent prognostic model for HCC patients. The IRRSM was shown to be positively correlated with the infiltration of four types of immune cells. CONCLUSION: Our results showed that some SIRGs have potential value for predicting the prognosis and clinical outcomes of HCC patients. IRGs affect the prognosis of HCC patients by regulating the tumor immune microenvironment (TIME). This study provides a new insight for immune research and treatment strategies in HCC patients.

A New Clinical Nomogram From the TCGA Database to Predict the Prognosis of Hepatocellular Carcinoma.

BACKGROUND AND AIM: Hepatocellular carcinoma is a common malignant tumor of the digestive system with a poor prognosis. The high recurrence rate and metastasis after surgery reduce the survival time of patients. Therefore, assessing the overall survival of patients with hepatocellular carcinoma after hepatectomy is critical to clinicians' clinical decision-making. Conventional hepatocellular carcinoma assessment systems (such as tumor lymph node metastasis and Barcelona clinical hepatocellular carcinoma) are obviously insufficient in assessing the overall survival rate of patients. This research is devoted to the development of nomogram assessment tools to assess the overall survival probability of patients undergoing liver resection. METHODS: We collected the clinical and pathological information of 438 hepatocellular carcinoma patients undergoing surgery from The Cancer Genome Atlas (TCGA) database, then excluded 87 patients who did not meet inclusion criteria. Univariate and multivariate analyses were performed on patient characteristics and related pathological factors. Finally, we developed a nomogram model to predict patient's prognosis. RESULTS: A retrospective analysis of 438 consecutive samples from the TCGA database of patients with hepatocellular carcinoma who underwent potentially curative liver resections. Six risk factors were included in the final model. In the training set, the discriminative ability of the nomogram was very good (concordance index = 0.944), and the external verification method (concordance index = 0.962) was used for verification. At the same time, the internal and external calibration of the model was verified, showing that the model was well calibrated. The calibration between the evaluation of the nomogram and the actual observations was good. According to the patient's risk factors, we determined the patient's Kaplan-Meyer survival analysis curve. Finally, the clinical decision curve was used to compare the benefits of two different models in evaluating patients' clinical outcomes. CONCLUSIONS: The nomogram can be used to evaluate the post-hepatectomy 1-, 3-, and 5-year survival rates of patients with hepatocellular carcinoma. The Kaplan-Meyer curve can intuitively display the survival differences among patients with various risk factors. The clinical decision curve is a good reference guide for clinical application.

Substituents and the induced partial charge effects on cobalt porphyrins catalytic oxygen reduction reactions in acidic medium.

Charge states at the catalytic interface can intensely alter the charge transfer mechanism and thus the oxygen reduction performance. Two symmetric cobalt porphyrins with electron deficient 2,1,3-benzothiadiazole (BTD) and electron-donating propeller-like triphenylamine (TPA) derivatives have been designed firstly, to rationally generate intramolecular partial charges, and secondly, to utilize the more exposed molecular orbitals on TPA for enhancing the charge transfer kinetics. The catalytic performance of the two electrocatalysts was examined for oxygen reduction reactions (ORR) in acidic electrolyte. It was found that BCP1/C with two BTD groups showed greater reduction potential but less limiting current density as compared to BCP2/C bearing BTD-TPA units. The reduced potential of BCP2/C was proposed to the introduction of the electron-donating ability of TPA, which may decrease the adsorption affinity of oxygen to the cobalt center. Both dipole-induced partial charge effect and the more exposed cation orbitals of the 3D structural TPA were proposed to contribute to the increased response current of BCP2/C. In addition, BCP2/C attained more than 80% of H2O2 generation in acidic solution, which may also relate to the structural effect. These findings may provide new insight into the structural design of organic electrocatalysts and deep understanding on the interfacial charge transfer mechanism for ORR.

Oroxylin A reversed Fibronectin-induced glioma insensitivity to Temozolomide by suppressing IP3R1/AKT/ß-catenin pathway.

AIMS: Cell adhesion mediated-drug resistance (CAM-DR) is one of main reasons for. the limitation to chemotherapy, but the underlying mechanism remains unclear in glioma. In this study, we investigated the mechanism of CAM-DR induced by Fibronectin (Fn). Besides, we studied the reversal effect of Oroxylin A, a natural flavonoid extracted from Scutellaria radix, on Temozolomide (TMZ) insensitivity of glioma cells. MAIN METHODS: Human Fn protein was used to mimic cell adhesion model and investigate its effect on the insensitivity of glioma cells to TMZ. Moreover, Oroxylin A was studied regarding its reversal effect on TMZ insensitivity of glioma via multiple molecular biological methods such as MTT, cell apoptosis assay, siRNA transfection, western blot, immunofluorescence assay. KEY FINDINGS: Fn could decrease the apoptosis-inducing effect of TMZ and led to the CAM-DR in glioma cells. Further studies showed that up-regulations of IP3R1 and intracellular Ca2+ level induced the activation of AKT kinase which increased the phosphorylation of GSK-3ß and subsequently caused the entry of ß-catenin into the nucleus. Knocking down IP3R1 significantly improved the sensitivity of glioma cells to TMZ. Meanwhile, after treatment with low-toxic concentration of Oroxylin A, the apoptosis induced by TMZ under Fn condition increased dramatically. Furthermore, our results revealed that Oroxylin A markedly inhibited the expression of IP3R1 and the activation of AKT/ß-catenin pathway. SIGNIFICANCE: Oroxylin A could reverse the insensitivity of TMZ via suppressing IP3R1/AKT/ß-catenin pathway and it might be helpful for enhancing the anti-cancer effect of TMZ in glioma.

Enhanced Oxygen Reduction Reaction Performance Using Intermolecular Forces Coupled with More Exposed Molecular Orbitals of Triphenylamine in Co-porphyrin Electrocatalysts.

Triphenylamine (TPA) has often been used as a building block to construct functional organic materials yet is rarely employed in oxygen reduction reaction (ORR) due to its strong electron-donating ability. This versatile segment bears a three-dimensional spatial structure whose effect has not been fully explored in catalytic systems. To this end, five symmetric cobalt porphyrins with carbazole and TPA derivatives have been synthesized and their ORR performance has been evaluated in acid medium. It was found that all compounds produced mainly hydrogen peroxide in oxygen reduction, with CP1 attaching benzyl derivatives and XCP4 possessing TPA-carbazole substituents at the meso-position of porphyrin, showing similar but more positive ORR potential as compared to the other analogues. Importantly, XCP4 achieved the greatest response current and the largest electron transfer numbers and H2O2 yields among the investigated molecules. Detailed electrochemical measurements suggested that the dipole-induced partial charges on the porphyrin in tandem with the more exposed molecular orbitals on TPA contributed to this enhancement, with the former attracting more protons to the affinity of reactive sites and the latter increasing the collision frequency between the electrocatalyst and H+ in solution. This is the first attempt to integrate the intermolecular forces with more exposed molecular orbitals in altering the electrochemical process.

An azido coumarin-quinoline conjugated fluorogenic dye: Utilizing amide-iminol tautomerism for H2S detection in live MCF-7 cells.

Detection of H2S to analyze some diseases in living lives demands fast response, high selectivity and biocompatibility. Here we designed an azide containing coumarin attached with 8-aminoquinoline via amide backbone (ACAQ) fluorophore as the H2S sensing probe. Excellent response time of 6 min, high sensitivity with the limit of detection (LOD) of 14.6 nM and high selectivity with other possible interferences are revealed for ACAQ after characterized by spectroscopy, 1H NMR titration and LC-MS measurements. The sensing strategy is explained by amide-iminol tautomerism and azide reduction. In addition, the successful visualization measurement suggests the practicability of the probe ACAQ for H2S detection in live samples.

Bimodal Molecule as NIR-CT Contrast Agent for Hepatoma Specific Imaging.

With currently available molecular imaging techniques, hepatocellular carcinoma (HCC), a liver cancer with high mortality rates and poor treatment responses, is mostly diagnosed at its late stage. This is largely due to the lack of highly sensitive contrast agents with high liver specificity. Herein, we report a novel bimodal contrast agent molecule CNCI-1 for the effective detection of HCC at its early stage both in vitro and in vivo. The agent has high liver specificity with effective X-ray computed tomography (CT)/near-infrared (NIR) imaging functions. It has been successfully applied to in vivo NIR imaging with high sensitivity and high selectivity to the HCC region of the HepG2 tumor-xenografted mice model and LM3 orthotopic hepatoma mice model. Moreover, the agent was found to be noninvasive and hepatocarcinoma cells preferential. Furthermore, it also enhanced the tumor imaging by revealing the blood vessels nearby for the CT image acquisition in the VX2 orthotopic hepatoma rabbit model. Our design strategy provides a new avenue to develop the medical relevant bimodal contrast agents for diagnosis of HCC at its early stage.

Effect of lymph nodes count in node-positive gastric cancer.

Background: The retrieved lymph node (LN) count has been confirmed as a prognostic indicator in various cancers. However, the correlation between LN counts and patient prognosis in gastric cancer with node-positive is not fully studied. Methods: A total of 8475 patients undergoing gastrectomy in Surveillance, Epidemiology, and End Results Program (SEER)-registered gastric cancer were analyzed. Kaplan-Meier methods and multivariable Cox regression models were used to analyze long-term outcomes and risk factors. Moreover, nomograms including LN counts were established to predict overall survival (OS) and cancer-specific survival (CSS), and Harrell's concordance index (c-index) was adopted to evaluate prediction accuracy. Results: Patients were stratified into 1-6, 7-14, and > 14 subgroups according to the optimal cutoff for retrieved LNs in terms of 5-year CSS. Further analysis indicated that higher LN counts were an independent predictor of longer survival in each N category. Nomograms on CSS and OS were established according to all significant factors, and c-indexes were 0.663 and 0.654 (P< 0.001), respectively. Conclusions: These results indicated that the more the LNs retrieved, the better the survival would be. Nomograms incorporating LN counts can be recommended as practical models to provide more accurate prognostic information for GC patients.

Integrated analysis of long noncoding RNA interactions reveals the potential role in progression of human papillary thyroid cancer.

Recent scientific evidence has suggested that long noncoding RNAs (lncRNAs) play an important part in tumorigenesis as an important member of competing endogenous RNAs (ceRNAs). Hundreds of RNA sequence data and relevant clinic information are freely accessible in The Cancer Genome Atlas (TCGA) datasets. However, the role of cancer-related lncRNAs in papillary thyroid cancer (PTC) is not fully understood yet. In this study, we identified 461 RNA sequencing data from TCGA. Subsequently, 45 lncRNAs, 21 miRNAs, and 78 mRNAs were chosen to construct a ceRNA network of PTC. Then, we analyzed the correlation between these 45 PTC-specific lncRNAs and clinic features and patient outcome. Thirty-seven of these lncRNAs were found to be closely related to age, race, gender, lymph node metastasis, TNM staging system, and patient outcome. Additionally, three of them were linked to PTC patient overall survival. Eventually, we selected eight lncRNAs randomly and performed quantificational real-time polymerase chain reaction (qRT-PCR) in 28 newly diagnosed patients with PTC to verify the reliability of the above results. The results of qRT-PCR are totally in agreement with the bioinformatics analysis. Additionally, it was found that HAND2-AS1 was negatively related to tumor size (P < 0.05). The results were consistent with the bioinformatics analysis in TCGA. Taken together, we identified the differentially expressed lncRNAs and constructed a PTC ceRNA network. The study provides a new perspective and supplement for our understanding of lncRNAs in PTC development and reveals potential diagnostic and prognostic markers in PTC.

Novel aromatic sulfonyl naphthalene-based boronates as 20S proteasome inhibitors.

A novel series of non-peptide proteasome inhibitors (PIs) that act on chymotrypsin-like (ChT-L) of the proteasome were developed. These PIs bearing 4-aromatic sulfonyl naphthalene-based scaffold and Leu-boronic moiety as covalent bonding group displayed far better activity than PI-8182 for inhibiting ChT-L in preliminary biological activity test. The results showed that 2a (IC50 = 6.942 µM, MCF-7) and 2c (IC50 = 6.905 µM, MCF-7) displayed higher anti-proliferative activities than Bortezomib (IC50 = 18.37 µM, MCF-7) under our experimental conditions. Furthermore, in the microsomal stability assay, 2a demonstrated excellent metabolic stability profiles with 56% remaining after 40 min, as compared to Bortezomib of which approximately 30% was remaining. The compounds 2a, 2c emerged as promising lead compounds for the development of novel non-peptide boronate PIs.

Risk Factors for Post-Transplant Death in Donation after Circulatory Death Liver Transplantation.

PURPOSE: In spite of the increasing success of liver transplantation, there remains inevitable risk of postoperative complications, re-operations, and even death. Risk factors that correlate with post-transplant death have not been fully identified. MATERIALS AND METHODS: We performed a retrospective analysis of 65 adults that received donation after circulatory death liver transplantation. Binary logistic regression and Cox's proportional hazards regression were employed to identify risk factors that associate with postoperative death and the length of survival period. RESULTS: Twenty-two recipients (33.8%) deceased during 392.3 ± 45.6 days. The higher preoperative Child-Pugh score (p = .007), prolonged postoperative ICU stay (p = .02), and more postoperative complications (p = .0005) were observed in deceased patients. Advanced pathological staging (p = .02) with more common nerve invasion (p = .03), lymph node invasion (p = .02), and para-tumor satellite lesion (p = .01) were found in deceased group. The higher pre-transplant Child-Pugh score was a risk factor for post-transplant death (OR = 4.38, p = .011), and was correlated with reduced post-transplant survival period (OR = 0.35, p = .009). Nerve invasion was also a risk factor for post-transplant death (OR = 13.85, p = .014), although it failed to affect survival period. CONCLUSIONS: Our study emphasizes the impact of recipient's pre-transplant liver function as well as pre-transplant nerve invasion by recipient's liver cancer cells on postoperative outcome and survival period in patients receiving liver transplantation.

Design, synthesis and biological evaluation of novel non-peptide boronic acid derivatives as proteasome inhibitors.

A novel series of non-peptide proteasome inhibitors bearing the 1, 4-naphthoquinone scaffold and boronic acid warhead was developed. In the biological evaluation on the chymotrypsin-like activity of human 20S proteasome, five compounds showed IC50 values in the nanomolar range. Docking experiments into the yeast 20S proteasome rationalized their biological activities and allowed further optimization of this interesting class of inhibitors. Within the cellular proliferation inhibition assay and western blot analysis, compound 3e demonstrated excellent anti-proliferative activity against solid tumor cells and clear accumulation of ubiquitinated cellular proteins. Furthermore, in the microsomal stability assay compound 3e demonstrated much improved metabolic stability compared to bortezomib, emerging as a promising lead compound for further design of non-peptide proteasome inhibitors.

[Protective effects of combined use of atorvastatin and low molecular weight heparin on the inflammatory reaction and pulmonary functions in rats with sepsis].

Objective: To investigate the influence of combined use of atorvastatin (ATO) and low molecular weight heparin (LMWH) on the inflammatory reaction and pulmonary protection functions in rats with sepsis. Methods: A total of 122 healthy male Sprague-Dawley (SD) rats were divided into five groups using a random number table: sham-operated group (sham group, n =10),sepsis group (n =10),ATO group (n =34),LMWH group (n =34),and ATO combined with LMWH group (ATO+LMWH group, n =34).The rat model of sepsis was reproduced by cecal ligation and puncture (CLP),while in sham group, rats were only subjected to laparotomy without cecum ligation and puncture. The rats of each pretreatment group received relevant therapies for 5 days, either gastric perfusion with ATO 20 mg/kg or subcutaneous injection with LMWH 100 U/kg or both before operation. The sepsis severities of the model animals were scored according to the modified sepsis severity assessment standards of experimental animals. Ten rats in each group were calculated the 7-day cumulative mortality rate. Blood samples from 6 rats in each group were collected to determine the levels of tumor necrosis factor-α (TNF-α),interleukin-1 ß (IL-1 ß) and high mobility group protein box-1 (HMGB1) contents in plasma using enzyme linked immunosorbent assay (ELISA)before operation (0 hour) and 4,8,12,and 24 hours post operation. The lung tissue was harvested 24 hours after operation, and the pulmonary pathology was assayed by hematoxylin and eosin (HE) staining using optical microscope. Results: ① The sepsis severity grades of sepsis group were significantly higher than those of sham group at 4 hours after operation (score:12.2 ± 2.0 vs.7.2 ± 0.5,P ＜ 0.05).Furthermore, they displayed a gradually increasing tendency, with the 7-day cumulative mortality rate being 90％ (9/10).The sepsis severity grades in ATO group, LMWH group, and ATO+LMWH group showed a significant decrease compared with sepsis group at 8 hours after operation (12.2± 2.0,11.2±2.2,10.0± 1.7 vs.16.6±2.5,all P ＜ 0.05).The 7-day cumulative mortality rates in ATO group, LMWH group, and ATO+LMWH group were 60％ (6/10),60％ (6/10),and 40％ (4/10),respectively, all of which was significantly lower than that of sepsis group (all P ＜ 0.05).② The levels of TNF-α,IL-1 ß and HMGB1 have not shown much variations in the sham group after operation; the levels of pro-inflammatory cytokines in other 4 groups were significantly increased after operation compared with those before operation; the levels of TNF-α,IL-1ß,and HMGB 1 reached peak at 4,8,and 24 hours, respectively. The levels of pro-inflammatory cytokines in sepsis group were significantly higher than those in the sham group. However, the levels of pro-inflammatory cytokines in ATO group, LMWH group, and ATO+LMWH group were significantly lower than those in sepsis group [4-hour TNF-α (ng/L):668.3 ± 124.6,536.5 ± 118.5,496.5 ± 108.5 vs.783.8 ± 134.7;8-hour IL-1 ß (ng/L):2 476.7 ± 137.8,2 460.4± 171.2,2 090.0 ± 151.2 vs.2 873.9 ± 295.6;24-hour HMGB1 (µg/L):654.4± 154.4,659.0± 134.6,609.4±90.5 vs.859.3 ± 167.5,P ＜ 0.05 or P ＜ 0.01].③ It was showed by optical microscopy that the pulmonary tissue morphology was normal in sham group and that the damage of pulmonary pathology was relatively severe in sepsis group. Compared with sepsis group, the damage of pulmonary pathology in ATO group, LMWH group, and ATO + LMWH group was alleviated obviously, and the most obvious improvements were found in ATO + LMWH group. Conclusions: Either ATO or LMWH could decrease sepsis severity, suppress the release of plasma pro-inflammatory cytokines at the early and late stages, alleviate the damage of pulmonary pathology, and reduce the 7-day cumulative mortality rate. Therefore, the combined treatment of sepsis using both ATO and LMWH resulted in better outcomes than implemented individually.

Inferior right hepatic vein-preserving major right hepatectomy for hepatocellular carcinoma in patients with significant fibrosis or cirrhosis.

BACKGROUND: Liver resection represents a most effective treatment for hepatocellular carcinoma (HCC). The extent of hepatectomy for HCC involves maintaining a tricky balance between radical resection of tumors and preservation of sufficient liver parenchyma. Generally, removal of the right hepatic vein often involves resection of the whole posterior right lobe, which may prevent patients with impaired liver function from maintaining a functional reserve and could also limit the future liver remnant from curative hepatectomy. As a common anatomic variation, preservation of the inferior right hepatic vein (IRHV) may enable preservation of liver segment 6, even when the right hepatic vein has to be removed. In the present study, we report our experience with IRHV-preserving major right hepatectomy. METHODS: From February 2009 to December 2011, eight trisegmentectomies 5-7-8 and two segmentectomies 4-5-7-8 were performed with the IRHV-sparing technique on patients with HCC and significant fibrosis or cirrhosis. Data including demographic information, preoperative evaluations, postoperative outcomes, and follow-up results were collected and evaluated. RESULTS: All patients survived and recovered from hepatectomy. The incidence of complications was higher in cirrhotic patients. The 1-year overall survival rate was 80 %, and the 1-year disease free survival rate was 60 %. CONCLUSIONS: IRHV-preserving major right hepatectomy increases the resectability of HCC. Intraoperative ultrasonography is recommended to facilitate protection of the IRHV. This technique is safe with careful preoperative evaluation and meticulous perioperative care. The short-term outcome of IRHV-preserving liver resections is satisfactory.

Systematic review: extracorporeal bio-artificial liver-support system for liver failure.

BACKGROUND: Orthotopic liver transplantation (OLT) is the only effective long-term treatment for liver failure by now. However, it is not yet a perfect choice due to donor-organ shortage and the need of a lifelong immunosuppressive therapy. Therefore, it is necessary to find a new approach to fighting the disease. Several published clinical trials have reported the therapeutic effect of bio-artificial liver (BAL) for liver failure. OBJECTIVE: To overview and evaluate the current clinical application and outcomes of extracorporeal BAL support system during the past 15 years. METHODS: Relevant studies were retrieved from PubMed and Cochrane Library databases. Independent assessments and the final consensus decision were performed by three independent reviewers. Acceptable study designs included randomized controlled trials, controlled clinical trials, and case reports. A total of 31 studies were tabulated and critically appraised in terms of characteristics, methods, and outcomes. RESULTS: There was a trend of falling into the normal ranges with the clinical and biochemical parameters after the BAL treatment. The neurological status of most patients was improved or stabilized during BAL treatment as well. No significant effect on survival could be seen after the BAL treatment. CONCLUSIONS: Although BAL system proved to be a success in some clinical cases reported, it still needs to be improved greatly.